PDA Microbiology Conference Update: Real Time Microbial Detection and Quality Control

Rapid microbiological methods (RMM) are utilized for a variety of applications, including in-process bioburden testing, environmental monitoring and finished product release for both sterile and non-sterile product. Recent advances in optical spectroscopic techniques now allow for the real-time detection, sizing and enumeration of microorganisms during volumetric air sampling. For the very first time, one of today’s sessions brought together three technology innovators that provide this type of instantaneous microbial detection capability. Following an introduction into the need for real-time monitoring that will support a QbD and PAT model for the parametric or real-time release of aseptically-filled, each innovator discussed the scientific and quality benefits, as well as contamination control opportunities that their technologies can provide.

I opened the session with a future vision for the real-time release of aseptically filled product. To realize this vision, I discussed the need for RMMs to be incorporated into the manufacturing process stream, providing real-time and continuous monitoring of in-process bioburden (e.g., pre- and post-filtration, and especially at the point of filling), in addition to real-time environmental monitoring. Additional considerations included the utilization of a robust manufacturing barrier system (e.g., an isolator or closed RABS), which would eliminate human-borne contaminants, as well as the incorporation of advanced aseptic filling technologies, such as blow-fill-seal and closed-vial filling technologies.

The next three presentations focused on real-time viable air monitoring technologies that are currently available to the pharmaceutical industry. Brief summaries and conclusions from each speaker are provided below.

IMD-A Systems for Instantaneous, Data-Rich Detection. Scott Morris, Applications Engineering Manager, BioVigilant

• A technical overview of two IMD-A instruments, validation data and potential applications were provided
• Continuous monitoring and technological sensitivity are a paradigm shift from traditional methods; these come with great benefits but will also require validation 
• Different applications and environments are unique; therefore, in-situ testing and qualification of optical spectroscopic/intrinsic fluorescence RMMs is key to success
• Data-rich feedback and software tools empower the end-user to extract relevant and actionable process knowledge, facilitating PAT and QbD, and allows the industry to move closer to real-time release

Real Time Viable Particle Detection: Key Capability and Application Considerations. Darrick Niccum, Global Product Manager-Biotechnology, TSI

• A technical review of TSI’s BioTrak Real Time Viable Particle Detector was provided
• This was followed by a review of laser induced fluorescence 
• Real time viable particle detection has great potential to improve pharmaceutical manufacturing process
• Some key performance parameters to consider include sample flow rate, aerosol efficiency, aerosol concentrator performance, an effective sampling rate, total particulate counting performance and discrimination capability

Application of Real-Time Microbial Monitoring in an Environmental Monitoring Program. Elizabeth Bennett, Microbiologist Application Scientist, Particle Measuring Systems

• A technical review of Particle Measuring System’s BioLaz Real-Time Microbial Monitor was provided
• Applications within filling lines, sterility test isolators, biosafety cabinets and during aseptic transfers was then discussed
• The benefits for using real-time environmental monitoring (EM) technologies include immediate notification for alarm response, the ability to partition finished product in the even of a microbial excursion (based on the timing of alarms), verification of acceptable biological levels prior to filling, faster batch release, reduced operator error and paperless data management
• Incorporation of this type of RMM into the existing EM program was further examined